Integrative bioinformatics and experimental analysis identify S100A10 as a diagnostic and prognostic biomarker in pancreatic adenocarcinoma.

Background: Pancreatic adenocarcinoma (PAAD) is an extremely invasive malignancy with limited effective treatment options. S100 calcium-binding protein A10 (S100A10), a protein-coding gene, plays a critical role in tumor progression. However, its correlation with immune cell infiltration and PAAD prognosis has not been previously reported. This study aimed to systematically explore the expression pattern, biological function and clinical value of S100A10 in PAAD. Methods: The expression of S100A10 in PAAD was investigated in a number of databases, including The Cancer Genome Atlas (TCGA), Tumor IMmune Estimation Resource 2.0 (TIMER 2.0), Gene Expression Omnibus (GEO), and the Human Protein Atlas (HPA). To evaluate the association between S100A10 expression and patient survival, both the Kaplan-Meier plotter and TCGA datasets were utilized. Furthermore, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, Gene Set Enrichment Analysis, and protein-protein interaction network evaluations were carried out to clarify the molecular mechanisms related to S100A10. Immune infiltration data were sourced from TCGA, and the methylation profile of S100A10 was evaluated using the UALCAN and MethSurv platforms. The expression levels of S100A10 were further confirmed in PAAD cell lines using quantitative reverse transcription polymerase chain reaction (PCR) and western blot analyses. To explore the functional implications of S100A10, assays including Cell Counting Kit-8 (CCK-8), wound healing, Transwell, and colony formation, were performed to assess its influence on the proliferation, migration, and invasion of PAAD cells. Results: The expression levels of S100A10 were notably elevated in PAAD compared with control group (P<0.05). S100A10 demonstrated high diagnostic precision, as evidenced by an area under the curve of 0.989, also with P<0.05. Higher levels of S100A10 correlated with poor prognosis in patients with PAAD. Cox regression analysis showed that S100A10 expression, tumor (T) stage, lymph node (N) stage, and histological grade were independent prognostic factors for overall survival (OS). A prognostic nomogram incorporating S100A10 expression was created to predict the patient outcomes. Functional analyses revealed that S100A10 was implicated in JAK-STAT and cytokine-cytokine receptor interaction pathways. Additionally, S100A10 was associated with humoral immune responses and DNA methylation processes, and hypomethylation of S100A10 was correlated with poor prognosis in PAAD. Immune infiltration analysis indicated that S100A10 expression was negatively correlated with various immune cell types. Furthermore, Conclusions: S100A10 is an oncogenic protein that promotes PAAD progression. Its elevated expression and hypomethylation status make it a promising diagnostic and prognostic biomarker for PAAD.